Quantitative regional assessment of lung function and structure has the potential to enhance early diagnosis and management of lung disease, and to provide more effective assessment of therapy. With this grant, we aim to develop regional quantitative techniques for measurement of lung function and structure in mice. We will utilize hyperpolarized helium-3 MRI technology to refine the apparatus and noninvasive technique for measuring lung ventilation, oxygenation and alveolar size in mice. The reproducibility and global validation of these imaging techniques will be conducted as part of this project. Furthermore we will systematically assess the sensitivity of each of these measurement techniques to presence and severity of a well-established inflammatory model of asthma in mice. In addition to studying sensitivity of these techniques to airway inflammatory response, we will study the correlation of these regional markers to gold standard measures of lung function and structure, namely pulmonary function testing and histopathology. The inherent heterogeneous characteristics of asthma suggests that imaging-based regional measurements of lung function and structure can potentially serve as more powerful tools in studying different aspects of this pulmonary disorder that may not be observable through global measurements of lung function. The ability to fully control ventilation parameters and repeat measurements with excellent reproducibility makes pulmonary imaging in small rodents very interesting. Such reproducibility is very hard to attain in larger animals. However, many of the currently existing hyperpolarized 3He MRI techniques - especially for measuring PAO2 - are not directly applicable in rodents and other small animals due to faster rate of physiological processes in these species, such as oxygen depletion rate, and physiological limitations on the length of breath-holds necessary for effective imaging. Thus the need for an established set of measurement tools to study regional aspect of rodent's pulmonary system, and specifically mice, is strongly felt in pulmonary research. Our group has recently developed methods that overcome these challenges, which by means of this grant, we aim to further refine. The central goal of this proposal is to develop, implement and refine hyperpolarized gas magnetic resonance imaging techniques to measure regional pulmonary ventilation (VA), partial pressure of oxygen (PAO2) and helium-3 apparent diffusion of coefficient (ADC) in the lungs of healthy mice, as well as in an established murine model of asthma. We will perform regional and overall correlation study between the measurements obtained from imaging and traditional non-imaging techniques, and attempt to quantitate the state of a the healthy and asthmatic mouse lung expressed in terms of these measurements. Keywords: Hyperpolarized Helium-3 MRI, Functional Pulmonary Imaging, Regional Lung Function, Regional Lung Structure, High Precision Rodent Ventilator, Regional Partial Pressure of Oxygen, Pulmonary Function Testing, Apparent Diffusion Coefficient, Regional Ventilation, Airway Remodeling. PUBLIC HEALTH RELEVANCE: To develop novel hyperpolarized helium-3 magnetic resonance imaging techniques for quantitative assessment of regional lung function and structure in mice. Assessment of the sensitivity of these techniques to airway remodeling induced by a murine model of asthma, compared to conventional pulmonary function tests, and validation of measurements against histological gold standard markers.